Cardiac hypertrophy in hypertension has been usually viewed in terms of adaptation to increased pressure load. Other factors however may play an important role in cardiac involvement in hypertensive diseases as suggested by our past observations that (a) increase in ventricular weight antidates hypertension in SHR and (b) hypertrophy can be prevented or even be reversed in SHR by alpha methyl dopa but not by hydralazine even though both drugs control arterial pressure equally. It is proposed to study the basic mechanisms responsible for differences between apparently equipotent antihypertensive drugs and their ability to reverse cardiac hypertrophy. Factors that might be involved might include reflex sympathetic stimulation of myocardium, alteration in renin, angiotensin and fluid balance and specific biochemical effects. Combination of specific adrenergic or angiotensin blockers and with deuretics may help elucidate the relative role of these various factors. Continuation of the studies correlating hemodynamic and biochemical alterations of SHR and the determination of the possible role of the sympathetic influence on performance of the hypertensive heart will be carried out by repeating the studies previously done but this time using autonomic blockade in both spontaneously hypertensive and renovascular hypertensive rats. A study of myocardial contractility is proposed by using papillary muscles and a correlation of these results with in vivo hemodynamics and biochemical changes before and after the reversal with in vivo hemodynamics and biochemical changes before and after the reversal of hypertrophy will be looked at. Determination of the specific effects of angiotensin antagonists on development of cardiac hypertrophy in the early stages of SHR when renin might still play a permissive role will also be studied.